Dysregulated CC receptor/ligand in monocytes/macrophages from tongue squamous cell carcinoma patients is partially rectified by interferon -2b Krishnendu Chakraborty a,,† , Anamika Bose a,,‡ , Kuntal K. Goswami a , Kalyan K. Mukherjee a,b , Shyamal Goswami a , Diptendu Ghosh a , Tathagata Chakraborty a , Koustav Sarkar a,§ , Smarajit Pal c , Anup Bhowmick d , Jaydip Biswas b,e , Rathindranath Baral a, * a Department of Immunoregulation and Immunodiagnostics, Chittaranjan National Cancer Institute, Kolkata 700026, India b Department of Medical Oncology, Chittaranjan National Cancer Institute, Kolkata 700026, India c Unit of Clinical Biochemistry, Chittaranjan National Cancer Institute, Kolkata 700026, India d Department of ENT & Head–Neck Oncology, Chittaranjan National Cancer Institute, Kolkata 700026, India e Department of Surgical Oncology, Chittaranjan National Cancer Institute, Kolkata 700026, India ARTICLE INFO Article history: Received 4 May 2011 Accepted 3 October 2011 Available online 29 October 2011 Keywords: Chemokines CCR5 IFN2b Monocytes Macrophages Tongue squamous cell carcinoma ABSTRACT In an aim to rectify dysregulated CC chemokine receptor (CCR5)/ligand (RANTES, MIP-1, MIP-1) status of monocytes/macrophages in tongue squamous cell carcinoma (TSCC; n = 12) patients, we have tested interferon 2b (IFN2b), a novel immunomodulator with wide use in the management of several forms of cancer. IFN2b can upregulate reduced CCR5 expression and increases the suppressed secretory status of its ligands, as evidenced from in vitro studies on monocytes/macrophages from the peripheral blood of TSCC patients as well as healthy individuals. Isolated monocytes of TSCC patients (n = 5) undergoing chemother- apeutic treatment along with IFN2b immunotherapy demonstrated significant upregulation in CCR5 ex- pression and secretion of corresponding ligands. These rectifications in receptor/ligand levels are reflected in improved CCR5-dependent migration of monocytes/macrophages after IFN2b treatment. The rectified chemokine profile and cellular migration translate into better tumoricidal and antigen-presenting functions of these cells. Accordingly, enhanced T-cell-mediated tumor cell killing is demonstrated upon IFN2b treatment. Translating dual benefits on monocyte/macrophage functions, IFN2b may emerge as a potential form of immunotherapy for TSCC patients that may be combined with standard chemotherapy for better clinical outcome.  2012 American Society for Histocompatibility and Immunogenetics. Published by Elsevier Inc. All rights reserved. 1. Introduction Head and neck squamous cell carcinoma (HNSCC), including tongue squamous cell carcinoma (TSCC), is a serious health prob- lem worldwide [1,2] and is also increasing in India [3]. Current therapeutic approaches with new-generation chemotherapy show promise, but overall increases in 5-year survival are insignificant [4]. Alternate approaches to combat this particular form of cancer are under evaluation [5,6]. Interferon -2b (IFN2b) is a pleotropic cytokine with wide applications in the treatment of several forms of cancer [7,8], including immunocompetent cancers [9,10] such as renal cell carcinoma and melanoma. TSCC, being a cancer of immu- nosuppressed type [11], is not generally considered for IFN2b immunotherapeutic protocols. However, our in vitro [12,13] stud- ies clearly suggested that this cytokine is effective to increase the tumoricidal efficacy of blood T cells, natural killer cells, and macro- phages (M) from HNSCC patients. Such in vitro results were ex- trapolated in a pilot in vivo study with immunosuppressed TSCC patients and significant immunopotentiation was noted in correla- tion with clinical outcome [14]. Monocytes (MO) and M are highly versatile, multifunctional cells characterized by their ability to engulf invading microbes or cell debris from injured sites, secrete a wide array of immuno- modulatory cytokines, and act as accessory cells in lymphocyte activation [15]. For T-cell-mediated killing, optimization of MO/M functions is important because they present antigens to T cells for initiation of antigen-specific tumor killing [16]. To actively assist antitumor T effector functions against tumor, MO/M should reach the tumor site with primary help from chemokines [17,18]. We previously reported dysregulated CXC chemokine signaling on T lymphocytes and their rectification by IFN2b was reported [19]. To ascertain the status of MO/M in chemotactic paths, we have selected the CC chemokine receptor CCR5 [20]. Studies have con- * Corresponding author. E-mail address: baralrathin@hotmail.com; baral.rathindranath@gmail.com (R. Baral). † Current address: Louisiana State University, Baton Rouge, LA 70803, USA. ‡ Current address: Department of Molecular Medicine, Bose Institute, C.I.T. Scheme, Kolkata, India. § Current address: Children’s Hospital of UPMC, Pittsburgh, PA 15224, USA. Human Immunology 73 (2012) 38-47 Contents lists available at SciVerse ScienceDirect 0198-8859/$36.00  2012 American Society for Histocompatibility and Immunogenetics. Published by Elsevier Inc. All rights reserved. doi:10.1016/j.humimm.2011.10.015